3,4-dicarbethoxy-{62 -phenethylcarbamic acid, ethyl ester in treating depression

ABSTRACT

A method of treating the symptoms of depression comprising administering a therapeutically effective amount of 3,4dicarbethoxy- Beta -phenethylcarbamic acid, ethyl ester to patients in need of such treatment.

United States Patent Plotnikoff 51 May 30, 1972 [54] 3,4-DICARBETHOXY-B- PHENETHYLCARBANIIC ACID, ETHYL ESTER IN TREATING DEPRESSION [72] Inventor: Nicholas Peter Plotnikofi, Lake Bluff, Ill.

[73] Assignee: Abbott Laboratories, North Chicago, Ill.

[22] Filed: Dec. 9, 1970 [21] App]. No.: 96,618

52 U.S. c1 ..424/300 51 lnt.Cl. [58] FieldoiSearch ..424/300 [5 6] References Cited OTHER PUBLICATIONS Chem. Abst. 69 35631 h (1968).

Primary Examiner-Stanley J. Friedman AttorneyRobert L. Niblack [57] ABSTRACT 2 Claims, No Drawings 3 ,4-DICARBETHOXY-B-PHENETHYLCARBAMIC ACID, ETHYL ESTER IN TREATING DEPRESSION This invention relates to a method for treating the symptoms of depression in mammalian patients using 3,4-dicarbethoxy-B-phenethylcarbamic acid, ethyl ester as the antidepressant agent.

Patients suffering from depression manifest one or more of a variety of symptoms. Generally speaking, depressed patients feel incapable of dealing with their responsibilities. The predominant symptoms of depression are hypochondria, andrexia, insomnia, anergia, anhedonia and pessism. Antidepressant drugs are being widely used to restore patients to a more normal state of mind and thus contribute to the patients physical and mental well-being. However, a number of the drugs produce a variety of undesirable side effects which limit their usefulness, particularly in children and in the elderly.

Accordingly, it is an object of this invention to provide a method for relieving the symptoms of depression in patients in need of such treatment without producing adverse side effects.

The compound useful in the practice of this invention, 3,4- dicarbethoxy-B-phenethylcarbamic acid, ethyl ester, is represented by the structural formula:

The compound can be prepared according to the method described in CA 69 3563 1h (1968). No utilities have previously been reported for the compound. It has now been found that the compound exhibits anti-depressant activity in test animals in dosages of from to 100 mg/kg of body weight daily.

The anti-depressant activity of the compound useful in the practice of this invention was first established using the modified dopa test described by Everett et al. The Search for New Anti-depressant Drugs, Fed. Proc., 23, p. 198 (1964). The modified dopa test is based on the following: when dl- DOPA is given to untreated mice, no response occurs because of the inactivation of the dopa by endogenous monoamine oxidase. However, if mice are pre-treated with a monoamine oxidase inhibitor, such as with the oral administration of 40 mg/kg of pargyline hydrochloride (Eutonyl), and are then given 200 mg/kg of dl-DOPA orally, along with a known antidepressant drug, the mice show maximal motor reaction with violent activity, jumping and fighting. Known anti-depressants such as imipramine and amintryptyline are extremely effective agents in potentiating the dopa response in mice. Thus, the modified dopa test has been found to be unusually sensitive and reliable in evaluating the anti-depressant activity of potential drugs. The response in the dopa test is graded l+for slight increase in activity, 2+ for moderate activity and 3+ for marked effects.

The following example illustrates this invention.

EXAMPLE 1 The anti-depressant activity of 3,4-dicarbethoxy-B- phenethylcarbamic acid, ethyl ester was evaluated in the above described modified dopa Test 4,8 and 24 hours after oral administration in mice. As can be seen from the following table, the compound exhibited moderate to marked antidepressant effects at dosages of from 5 to 100 mg/kg of body weight. The oral and intraperitoneal LD of the compound in mice is 1000 mg/kg.

TABLE I Anti-Depressant Activity of 3,4-Dicarbethoxy-[3-Phenethyl- Carbamic Acid, Ethyl Ester 4,8 and 24 Hours After Oral In the practice of this invention, patients suffering from depression receive from 5 to 100 mg/kg of body weight daily of 3,4-dicarbethoxy-B-phenethylcarbamic acid, ethyl ester, either in single or divided doses. While the compound exhibits activity by both oral and parenteral routes, oral administration is preferred.

While the compound can be administered alone, that is, for example, as the sole ingredient in a filled capsule, it is preferred that the active agent be formulated into a pharmaceutically acceptable dosage form as is customary in the 811.

Solid dosage forms for oral administration include capsules, tablets, pills, powders and granules. In such solid dosage forms, the active compound is admixed with at least one inert diluent such as sucrose, lactose or starch. Such dosage forms can also comprise, as is normal practice, additional substances other than inert diluents, e.g., lubricating agents such as mag- 3 nesium stearate. In the case of capsules, tablets and pills, the

dosage forms may also comprise buffering agents. Tablets and pills can additionally be prepared with enteric coatings.

Liquid solutions, suspensions, dosage forms for oral administration include, pharmaceutically acceptable emulsions, 35 solutipins, syrups, and elixirs containing inert diluents commonly used in the art, such as water. Besides inert diluents, such compositions can also include adjuvants, such as wetting agents, emulsifying and suspending agents, and sweetening, flavoring and perfuming agents.

Preparations according to this invention for parenteral administration include sterile aqueous or non-aqueous solutions, suspensions or emulsions. Examples of non-aqueous solvents or vehicles are propylene glycol, polyethylene glycol, vegetable oils, such as olive oil and injectable organic esters such as ethyl oleate. Such dosage forms may also contain adjuvants such as preserving, wetting, emulsifying and dispersing agents. They may be sterilized by, for example, filtration through a bacteria-retaining filter, by incorporating sterilizing agents into the compositions, by irradiating the compositions, or by heating the compositions. They can also be manufactured in the form of sterile solid compositions which can be dissolved in sterile water, or some other sterile injectable medium immediately before use.

Compositions for rectal administration are suppositories which may contain in addition to the active substance, excipients such as cocoa butter or a suppository wax.

The dosage of active ingredient in the compositions of this invention may be varied; however, it is necessary that the amount of the active ingredient shall be such that a suitable dosage form is obtained. The selected dosage depends upon the desired therapeutic effect, on the route of administration, and on the duration of the treatment.

I claim 1. A method of treating a patient exhibiting the symptoms of depression comprising administering a therapeutically effective amount of 3,4-dicarbethoxy-B-phenethylcarbamic acid, ethyl ester, to a depressed patient.

2. A method in accordance with claim 1 wherein the compound is administered to a depressed patient in dosages of 70 from 1 to 100 mg./kg. of body weight daily. 

2. A method in accordance with claim 1 wherein the compound is administered to a depressed patient in dosages of from 1 to 100 mg./kg. of body weight daily. 